tbuckley/cabot-search huggingface dataset:
Preliminary clinical investigations of high-dose furmonertinib in NSCLC with EGFR Exon 20 insertions (20ins).
Authors: Ying Lin, Zhihuang Hu, Yao Zhang, Si Sun, Hui Yu, Xinmin Zhao, Xianghua Wu, Huijie Wang, Jialei Wang
Journal: Journal of Clinical Oncology (2022)

e21029 Background: Currently neither chemotherapy nor approved EGFR TKIs have satisfactory efficacy in most EGFR 20ins mutations. Activity of high-dose furmonertinib, a novel 3 rd generation EGFR TKI, against EGFR 20ins was assessed in preclinical models and a phase lb study. This study aimed to retrospectively investigate the efficacy of high-dose furmonertinib against EGFR 20ins in the real world. Methods: Retrospective search identified 14 metastatic NSCLC patients (pts) with EGFR 20ins treated with high-dose furmonertinib (160mg qd) in Fudan University Shanghai Cancer Center. The clinical efficacy and safety were investigated. Results: Median age was 60 years old (range 40-75) in this cohort with 28% female. At data cutoff date of January, 2022, 9 pts had ≥1 disease assessment. 5 out of 9 pts achieved PR, and 3 patients achieved SD. No CR was observed and 1 patient PD at first assessment. The most common adverse events (AE, ≥20%) were diarrhea, paronychia, skin fissures, anorexia, pain in extremity, rash and stomatitis. No grade ≥3 AE was observed. Conclusions: High-dose furmonertinib has shown encouraging anti-tumor activity in NSCLC with EGFR 20ins.
QOL-14. Long term neurocognitive and psychosocial outcomes among adolescents and young adults survivors of paediatric brain tumour.
Authors: Sonia Di Profio, Sara De Giuseppe, Sabrina Robotti, Miriana Uccello, Marco Crocco, Antonio Verrico, Gianluca Piccolo, Camilla Satragno, Claudia Milanaccio, Cristina Venturino, Maria Luisa Garrè
Journal: Neuro-Oncology (2022)

Abstract PURPOSE: The aim of the study was to describe neurocognitive and psychological outcomes among adolescents and young adults (AYA) survivors of paediatric brain tumour (BT). METHODS: neurocognitive and psychological assessment of 45 AYA (M = 30; F = 15), treated for paediatric BT at our institution between 1978 and 2018, were retrospectively collected. Survivors received psychological and neurocognitive assessment at a mean age of 21.4 years (range 15.11-39.4) after a median of 120 months from diagnosis. The assessment was carried out using the following self-report questionnaires: Beck Depression Inventory, State-Trait Anxiety Inventory, Body Uneasiness Test, Multidimensional Fatigue Inventory, European Organization for the Research and Treatment of Cancer Quality of LifeQuestionnaire. Neurocognitive evaluation was carried out using Wechsler Adult Intelligence Scale. RESULTS: 18/45 survivors had received a diagnosis of germ cell tumor, 12 of low grades glioma, 10 of embryonal tumor, 3 of high-grade glioma, 2 of meninges and mesenchymal tumor. Thirty-four patients received neurosurgery, 34 patients chemotherapy, 44 patients cranial radiotherapy. Fatigue was reported in 56% of the patients, 15% of them also showed low level of QoL. The psychological assessment showed clinical levels of anxiety in 56% of AYA, depression in 41% and body image problems in 29%. Neurocognitive assessment showed that 73% has an average tIQ (tIQ ≥ 80). CONCLUSIONS: The psychological evaluation showed that 77% of our cohort had at least one clinically significant distress symptom as fatigue, depressive symptoms, anxiety and body image problems, compared to 23% who did not report any problem. Further analysis is needed to identify any possible psychopathological risk factors. It is essential to provide an accurate and comprehensive assessment and effective psychological support to these patients, to help them better manage the late effects of cancer and therapies at different levels: physical, psychological and neurocognitive.
Is BMD (Bone Mineral Density) a prognostic factor for luminal A breast cancer in postmenopausal women?
Authors: Seungju Lee, Hyun Yul Kim
Journal: Journal of Clinical Oncology (2022)

e12542 Background: There are some studies concerned about the relationship of BMD (Bone Mineral Density) and breast cancer risks in menopausal women. However, most studies have limitations in that they did not distinguish the subtypes of breast cancer. Therefore, we assessed the BMD as a risk factor of recurrences, metastases, or occurrences of contralateral breast cancer in the luminal A breast cancer patients with menopause. Methods: In this retrospective study, the data of 348 luminal A type breast cancer patients, who underwent treatment at the Pusan National University Yangsan Hospital from 2012 to 2016, were analyzed. BMD of the lumbar spine, total femur, and femoral neck was measured by Dual Energy X-ray Absorptiometry (DXA). According to the measured BMD and WHO criteria, the group with T scores ≥ -1.0 was defined as normal, the group with T scores &lt; -1.0 and &gt; -2.5 was defined as osteopenia, and the group with T scores &lt; -2.5 was defined as osteoporosis. The patients were divided into two groups: those with normal BMD and those with low BMD including osteopenia or osteoporosis in preoperative examination. We also divided patients as three groups: one group with no change of BMD, the other group with improvement of BMD and the other with deterioration of BMD during treatment. We used Chi-squared tests, Kaplan-Meier method and Cox-regression model to analyze the relationship between BMD and breast cancer risk. Results: Among the 348 patients, normal BMD was confirmed by preoperative examination in 129 patients and low BMD was identified in 219 patients. There was no change in BMD during the treatment in 243 patients. The improvement in BMD was identified in 37 patients, and the deterioration of BMD was confirmed in 68 patients. Younger patients were distributed in normal BMD compared to low BMD (55.7±6.9 vs 61.8±8.0, p&lt;0.05). There were only 14 patients (4.0%) with recurrences, distant metastases or occurrences of contralateral breast cancer during a median follow-up period of 78 months. Among the 219 patients with low BMD, disease-free survival at 5 years was 98.2% compared to 95.0% for 129 patients with normal BMD ( p=0.326). In addition, disease-free survival at 5-years was 97.0% in no change of BMD during treatment, 94.6% in improvement of BMD, and 98.4% in deterioration of BMD ( p=0.785). Conclusions: In this study, BMD did not have statistically significance in the recurrences, metastases, or occurrences of contralateral breast cancer in luminal A breast cancer patients with menopause. In addition, there was no statistically importance in relationship between BMD change during treatment and recurrences, metastases, or occurrences of contralateral breast cancer. Therefore, we should perform treatments to breast cancer patients preventing decreased BMD.
Effects of interventions on cerebral perfusion in the Alzheimer's disease spectrum: A systematic review
Authors: Sofia Marcolini, Ingeborg Frentz, Carlos A. Sanchez-Catasus, Jaime D. Mondragon, Paula Kopschina Feltes, Anouk van der Hoorn, Ronald J.H. Borra, M. Arfan Ikram, Rudi A.J.O. Dierckx, Peter Paul De Deyn
Journal: Ageing Research Reviews (2022)

Cerebral perfusion dysfunctions are seen in the early stages of Alzheimer's disease (AD). We systematically reviewed the literature to investigate the effect of pharmacological and non-pharmacological interventions on cerebral hemodynamics in randomized controlled trials involving AD patients or Mild Cognitive Impairment (MCI) due to AD. Studies involving other dementia types were excluded. Data was searched in April 2021 on MEDLINE, Embase, and Web of Science. Risk of bias was assessed using Cochrane Risk of Bias Tool. A meta-synthesis was performed separating results from MCI and AD studies. 31 studies were included and involved 310 MCI and 792 CE patients. The MCI studies (n = 8) included physical, cognitive, dietary, and pharmacological interventions. The AD studies (n = 23) included pharmacological, physical interventions, and phytotherapy. Cerebral perfusion was assessed with PET, ASL, Doppler, fNIRS, DSC-MRI, Xe-CT, and SPECT. Randomization and allocation concealment methods and subject characteristics such as AD-onset, education, and ethnicity were missing in several papers. Positive effects on hemodynamics were seen in 75 % of the MCI studies, and 52 % of the AD studies. Inserting cerebral perfusion outcome measures, together with established AD biomarkers, is fundamental to target all disease mechanisms and understand the role of cerebral perfusion in AD.
LINC-21. PROGNOSTIC FACTORS AND SURVIVAL OF LOW-GRADE GLIOMAS IN CHILDREN AND ADOLESCENTS – A MULTICENTER STUDY IN PERU
Authors: Rosdali Diaz-Coronado, Eddy Hernández-Broncano, Sandro Casavilca-Zambrano, Danny Campos-Sanchez, Ivan Maza, Mariela Tello, Esmeralda Leon, Hernan Cañari, Javier Custodio, Luis Ojeda-Medina, Tatiana Negreiros, Olga Cordova, Pamela Mora-Alferez, Juan Garcia-Leon, Liliana Vasquez, Daniel Moreira, Ibrahim Qaddoumi
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND: Low-grade gliomas (LGG) are the most common central nervous system (CNS) tumors in children. Peru is an index country for the Global Initiative for Childhood Cancer (GICC). As part of the Initiative, a multidisciplinary brain tumor team was formed in 2020 that includes five national reference centers: National Institute of Neoplastic Diseases, National Children’s Health Institute-San Borja, National Children’s Health Institute-Breña, Edgardo Rebagliati Martins National Hospital and Guillermo Almenara Irigoyen National Hospital. This multicenter study sought to evaluate the survival and prognostic factors of patients younger than 18 years diagnosed with LGG, an index cancer for the GICC. METHODS: A retrospective study included all patients diagnosed with LGG in the five centers between 2014 and 2018. We analyzed clinical characteristics, histology, and treatment modalities. We used the Kaplan-Meier method for survival. RESULTS: 194 patients were registered; 136 patients were included. M/F ratio was 1.2, mean age 7 years old. The most frequent location was infratentorial (42.2%), supratentorial (34.9%), optic/chiasm/sellar (11%) and brainstem (11.9%). The most frequent histological types were pilocytic astrocytoma (61%), diffuse astrocytoma (10.3%), oligodendroglioma (5.2%), and other low-grade neoplasms (23.5%). Surgery was performed in 109 patients (83.2%). Chemotherapy alone was used in 17 (12.5%), while radiotherapy in 20 (14.7%). Overall survival at 5 years was 82.9% (95% CI 73.3 - 89.4). Age younger than 3 years (p=0.002), diffuse histological type (p=0.04), and location in the brainstem (p=0.001) were factors associated with a worse prognosis. CONCLUSIONS: Within the framework of the GICC, this work is one of the first steps to understand the current context of pediatric CNS tumor care in Peru. Although the reported survival rate is about the GICC goal of 60%, further improvements in care are needed to increase survival to level closer to high-resource setting and decrease long term morbidity.
A phase II trial of ALK/ROS1 tyrosine kinase inhibitor WX-0593 (iruplinalkib) in <i>ALK</i>-positive and crizotinib-resistant advanced non–small cell lung cancer.
Authors: Yuankai Shi, Jianhua Chen, Helong Zhang, Zhihong Zhang, Yiping Zhang, Zhehai Wang, Shucai Zhang, Jian Zhao, Chunling Liu, Xiuwen Wang, Yanqiu Zhao, Changlu Hu, Lei Yang, Xuezhi Hao, Lin Wang, Meimei Si, Mingjing Ge, Huaize Geng
Journal: Journal of Clinical Oncology (2022)

9073 Background: This single-arm, multicenter phase II trial aimed to evaluate the efficacy and safety of second generation ALK/ROS1 TKI WX-0593 (iruplinalkib) in advanced ALK/ ROS1-positive non-small cell lung cancer (NSCLC). We reported the results from the crizotinib-resistant ALK-positive cohort. Methods: Patients aged ≥18 years, with histologically or cytologically confirmed ALK-positive NSCLC, progression on ≥12-week crizotinib treatment, ≥one measurable lesion according to RECIST v1.1, and ECOG PS of 0 to 2 were eligible. Patients received oral WX-0593 180 mg once daily (with a 7-day lead-in period at 60 mg once daily). The primary endpoint was confirmed overall response rate (ORR) by independent review committee (IRC) per RECIST v1.1. Secondary endpoints included confirmed disease control rate (DCR) by IRC, ORR, DCR, duration of response (DoR), progression-free survival (PFS), time to progression (TTP), intracranial ORR (iORR) per RANO-brain metastases criteria by investigator (INV), overall survival (OS), safety, and C max,ss . Results: Between August 7, 2019 and October 30, 2020, totally 146 patients were enrolled. The data cutoff date was March 10, 2021. The median follow-up was 9.3 months (IQR 6.3-14.1). 90 (61.6%) patients had brain metastases, of which 41 (46%) had measurable intracranial lesions and 20 (22%) received prior radiotherapy to brain. 56 (38.4%) patients received prior chemotherapy. The IRC-assessed ORR was 67.8% (95% CI 59.6%-75.3%). Efficacy data were detailed in the Table. Additionally, subgroup analyses indicated IRC-assessed ORR were slightly higher in the patients without brain metastases (79% vs 61%) or prior radiotherapy to brain (66% vs 45%). Patients with prior chemotherapy or not had similar results (71% vs 66%). The iORR was 63% (95% CI 47%-78%) in pts with measurable intracranial lesions. OS data were immature. 134 (91.8%) of 146 experienced treatment-related adverse events (TRAEs). The most common TRAEs were AST increased (60 [41.1%]), ALT increased (52 [35.6%]), and blood creatine phosphokinase increased (49 [33.6%]). Dose reduction and discontinuation due to TRAE, and serious TRAEs occurred in 15 (10.3%), three (2.1%), and six (4.1%), respectively. No treatment-related death was reported. Drug concentration reaches steady state at Day 21 (C max,ss =255.4 ng/mL). Conclusions: WX-0593 showed promising activity against ALK-positive NSCLC after crizotinib resistance and favorable safety profile, demonstrating WX-0593 could be a new treatment option for this patient population. Clinical trial information: NCT04641754. [Table: see text]
Investigate the accuracy and economic value of the upstaging prediction model for ductal carcinoma in situ.
Authors: Ching-Wen Chiu, Ka-Wai Tam, Shen Liang Jerry Shih
Journal: Journal of Clinical Oncology (2022)

e12577 Background: The current study aims to define the “high-risk upstaging model” in ductal carcinoma in situ (DCIS) and investigate its accuracy in order to suggest the most precise application of sentinel lymph node biopsy (SLNB). Methods: PubMed, EMBASE, and Cochrane library databases were searched. Prospective and retrospective cohort studies that evaluated the pathological outcomes of SLNB and the upstaging rate in women with DCIS were included. We analyzed factors that potentially indicate nodal involvement risk and combine the significant ones into “high-risk upstaging model”. Consecutively, we conducted a retrospective study by applying our model and NCCN guideline model into DCIS patients extracted from hospital database. Both the excess treatment rate and incomplete treatment rate of SLNB were analyzed. The diagnostic performance of the model in predicting upstaging risk was evaluated with receiver operating characteristic (ROC) curve. Results: We retrieved 43 prospective and 69 retrospective studies including 44,001 DCIS patients. The upstaging rate was significantly higher in patients with estrogen receptor-negative status, palpable mass, tumor size &gt; 2 cm on imaging, and high-nuclear grade and those who received a preoperative diagnosis through core needle biopsy. We then collected 168 DCIS patients who entered in Shuang-Ho hospital from February 2017 to August 2021. Ninety-six patients who didn’t upstage in final pathology have received extra SLNB and two patients who upstaged in final pathology did not receive SLNB in primary surgery. The areas under the ROC curve of the model developed by multivariable logistic regression for predicting upstaging risk in the NCCN guideline group and “high-risk upstaging model” group were 0.642 and 0.706, the sensitivity at 66.0% and 83.0%, and the specificities at 62.5% and 49.2%, respectively. Conclusions: “High-risk upstaging model” shows higher areas under the ROC curve and sensitivity as well compared with current NCCN guideline. Our prediction model can provide surgeons with a more accurate and specific indications of SLNB in DCIS.
over-activated p21 protein activated kinase-3 (pak3) leads to myocardial lipotoxicity and cardiac dysfunction in diet-induced metabolic stress
Authors: W Liu, A Ruiz-Velasco, R Raja, N Kaur
Journal: Cardiovascular Research (2022)

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): British Heart Foundation Background In clinics, metabolic stress-induced cardiomyopathy is featured as diastolic/systolic dysfunction, at least partially resulting from impairment of metabolic flexibility in the myocardium, which leads to lipotoxicity and oxidative stress accompanied with cardiomyocytes death. P21-activated kinases (Paks) are a family of serine/threonine kinases, involved in cell survival, proliferation and cytoskeleton remodelling. In spite of the cardioprotective functions of Pak1 and Pak2 in the myocardium, the role of cardiac Pak3 is unexplored. Purpose The study is to investigate the function of cardiac Pak3 on myocardial steatosis in response to diet-induced metabolic stress, which will provide proof-of-concept evidence for the therapeutic potential for alleviating cardiac dysfunction by targeting lipotoxicity in the myocardium. Methods Pak3 overexpression in the myocardium was achieved by tail vein injection of adeno associated virus (AAV9) delivery of troponin T promoter-driven Pak3 on C57BL/6J mice. The mice were fed with high fat high sucrose diet, the metabolic profiles and cardiac function were measured at 4-week intervals. In addition, cardiac morphological and cellular changes were assessed, including cell size, fibrosis formation, cell death, lipid accumulation and lipid peroxidation. In addition, the transcript levels of the genes either participating lipid metabolism or regulating oxidative stress were also assessed by qPCR. Results First, we detected that Pak3 expression and activation was increased in the myocardium from human with obese or diabetes. Consistently, the augmented Pak3 was also detected in the failing heart from C57BL/6J mice, ob/ob and db/db mice. Next, in a time-course study, the mice with AAV9-delivery cardiac Pak3 overexpression were vulnerable to cardiac dysfunction upon diet-induced metabolic stress. Pak3 overexpression did not alter cardiomyocyte size; however, more fibrosis and cell death in the myocardium were detected due to Pak3 enhancement. More importantly, myocardial lipid accumulation and profound lipid peroxidation were determined by immunefluorescent staining of Perilipin 5 (PLIN5) and 4-Hydroxynonenal (4-NHE), respectively. Finally, the abnormal expression of the genes involved in lipid synthesis and fatty acid oxidation was detected in Pak3-overexpressed myocardium under metabolic stress, whereas the levels of anti-oxidative stress genes were decreased. Conclusion Altogether, the study has demonstrated that Pak3 over-activation makes the heart more susceptible to myocardial lipotoxicity, which accelerates cardiac steatosis and dysfunction in the fact of metabolic stress.
The association of Ki67 level and adjuvant treatment options in mucosal melanoma.
Authors: Xiaoting Wei, Lirui Tang, Caili Li, Xue Bai, Lili Mao, Zhihong Chi, Chuanliang Cui, Bin Lian, Bixia Tang, Yu Du, Xuan Wang, Xinan Sheng, Xieqiao Yan, Siming Li, Li Zhou, Yan Kong, Jie Dai, Jun Guo, Lu Si
Journal: Journal of Clinical Oncology (2022)

e21582 Background: Both chemotherapy and high-dose IFN-α2b (HDI) are effective treatment options in adjuvant setting for patients with resectable mucosal melanoma (MM). However, it is still unknown whether Ki67 level affects the selection of chemotherapy and HDI. Methods: Data from resected MM patients diagnosed as MM in Peking Cancer Hospital, were retrospectively collected and analyzed. Key inclusion criteria were: (1) diagnosed as resectable MM, with the date between Jan. 1, 2010, and Dec. 31, 2018; (2) Ki67 was identified by immunohistochemical staining; (3) received TMZ-based adjuvant chemotherapy or HDI. All patients were divided into two subgroups according to the Ki67 level proposed by previous publications: low (&lt; 30%), high (&gt; = 30%). Relapse-free survival (RFS) and melanoma-specific survival (MSS) were compared across different subgroups by log-rank tests. Multivariate Cox proportional hazards models were used to calculate hazard ratios (HRs), controlling for age, sex, primary site, lymphatic metastasis, LDH level, and gene mutational status (BRAF, c-KIT and NRAS). Results: In total, 1106 MM patients were screened and 175 met the inclusion criteria for analysis. 100 and 75 patients received temozolomide (TMZ)-based adjuvant chemotherapy and HDI therapy, respectively. Patients who received adjuvant chemotherapy had a superior RFS (21.0 vs. 9.6 months, HR = 0.47, P = 0.002) as compared to those with HDI, but no significant difference for MSS (45.9 vs. 37.6 months, HR = 0.63, P = 0.396). Longer RFS and MSS were observed in the ki67-low subgroup (HRs were 0.51, 95%CI 0.34-0.76 and 0.41, 95%CI 0.24-0.68 for RFS and MSS, respectively). For patients with low Ki67 (&lt; 30%), two regimens showed no statistically different RFS (33.9 vs. 22.7 months, HR = 0.76, P = 0.329) and MSS (114.5 vs. 61.4 months, HR = 1.23, P = 0.967). However, for those with high Ki67, TMZ-based chemotherapy achieved an extended RFS compared with HDI (18.0 vs. 6.7 months, HR = 0.36, P &lt; 0.001) and a trend toward improvement for MSS (41.4 vs. 25.1 months, HR = 0.47, P = 0.067). Conclusions: Ki67 level is an independent negative prognostic factor and impacts the selection of adjuvant treatment options for MM patients. Chemotherapy should be considered as the preference for patients with Ki67 &gt; = 30%.
Outcomes Among Patients With 1-Year Survival After Intensive Care Unit Treatment for COVID-19
Authors: Carla M. Sevin, E. Wesley Ely
Journal: JAMA (2022)

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Step by step 3D virtual models assistance in case of complex robotic partial nephrectomies
Authors: A. Pecoraro, F. Piramide, P. Verri, E. Checcucci, S. De Cillis, A. Piana, M. Manfredi, C. Fiori, F. Porpiglia, D. Amparore
Journal: European Urology (2022)
Erectile dysfunction and impaired sexual quality of life in men with overactive bladder: A single cohort analysis
Authors: V. Iacovelli, M. Carilli, M. Antonucci, F. Petta, C. Cipriani, R. Bertolo, F. Maiorino, M. Signoretti, M. Vittori, E. Finazzi Agrò, P. Bove
Journal: European Urology (2022)
Evaluation of an uncomplicated recovery after nephrectomy: MUSIC-KIDNEY NOTES (Notable Outcomes and Trackable Events after Surgery)
Authors: M. Butaney, A. Johnson, J. Qi, A. Patel, S. Noyes, C. Brede, B. Seifman, T. Maatman, C.G. Rogers, B.R. Lane
Journal: European Urology (2022)